Natural Orifice Transluminal Endoscopic Surgery (NOTES) is an emerging technology that allows a surgeon to insert surgical instruments through a natural orifice (such as the mouth, anus, or vagina) and then access the abdominal cavity through a defect created in the stomach, colon, bladder or vagina, thus avoiding any external incisions or scars. NOTES has been performed on experimental pig models using various surgical procedures and flexible endoscopy instruments. A major hurdle to transform this technology to the human patient is the closure of the luminal defect created to access the abdominal cavity. Suture closure is still the preferred means of closing such a luminal defect, but is technically challenging because of space constraints in the endoscope. Furthermore, when creating an incision through the gastrointestinal tract, whether it is the stomach or the colon, a subsequent leak could lead to catastrophic problems, and thus, reliability of the closure is of utmost concern.